Pleiotropic effects of statins

Abstract

The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. Additionally, in adequately powered trials, total mortality has been successfully decreased by the use of statin therapy. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. The causal theory of pharmacologic benefit reiterates the lipid hypothesis, which states that dyslipidemia is central to the process of atherosclerosis and the clinical benefit which accrues from statin therapy is a function of the degree of lipid lowering. The noncausal theory supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability) as being the major modulators of clinical benefit. This review will focus on the potential beneficial effects of statin therapy on a number of the pleiotropic effects of statins and the potential role that these activities play in the reduction of risk for ischemic events.

Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects

“…Beneficial effects of statins on BP control and endothelial function are well established. 17,18 However, the concomitant medications including statins were not changed throughout the study period. Thus, improvement of BP control and brachial artery FMD in the treatment group may be explained by low-dose aspirin administration.…”

Statins as Immunomodulatory Agents

“…7 However, because mevalonate, the product of the enzyme reaction, is the precursor not only of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of HMG-CoA reductase may produce pleiotropic effects. [7][8][9][10][11] Indeed, the mevalonate pathway yields a series of isoprenoids that are vital for diverse cellular functions. 8 These isoprenoids include: isopentenyl adenosine, present in some types of transfer of RNA; dolichols, required for glycoprotein synthesis; and polyisoprenoid side chains of ubiquinone and heme A, involved in electron transport.…”

Effects of statins on the prognosis of local and locally advanced renal cell carcinoma following nephrectomy

“…Statins have been shown to attenuate vasoconstriction by increasing endothelial nitric oxide activity (15). Thus, they have pleiotropic cardiovascular and anti-atherosclerotic effects, including improvement of endothelial function, reduction of free radical formation, stabilization of plaques and inhibition of endothelial inflammatory reactions, which contribute to other potential benefits for patients at risk of cardiovascular disease, regardless of cholesterol levels (8,16). The mechanisms of these antitumor effects have yet to be fully elucidated.…”